Transcript

Jane Barrett: He said ‘you have cancer, you have a cancer that can’t be identified and it’s spread from somewhere in your body’. That’s the triple whammy, people get diagnosed with cancer, this is a metastatic cancer, that is it’s spread from somewhere and we can’t tell where it’s come from.

David Bowtell: It’s in the top ten causes of cancer deaths in Australia it’s ranked currently around third or fourth.

Penny Schofield: It’s a very hard to understand diagnosis, it’s very frightening because doctors are confused about what to do about it. There are very, very few effective treatments, there’s no research to guide diagnosis or treatment and patients end up feeling fairly hopeless, fearful and I think also most abandoned.

Norman Swan: What we’re talking about here doesn’t have a proper name because no one is too sure what the malignancy actually is. It’s called Cancer of Unknown Primary, CUP, it’s common, it often has bad outcomes, there’s pitifully little research going on but as you’ll hear, thanks largely to the efforts of one woman, Jane Barrett, that’s changing.

Jane Barrett: The first major thing was a lump on the right side of my neck which came up in October 2008. But prior to that I’d had some extremely vague symptoms over a period of maybe two years of clearing my chest, clearing my throat, a slight cough, but all so vague you could put it down to anything. And then came a slight feeling in the back of my throat just when I swallowed of just something being there but it was easier to forget. The real worry came in October 2008 when the lump came and I went to the doctor and the doctor didn’t mention anything suspicious. I had a CT scan that reported an enlarged lymph node, but there was no mention of cancer. So I just put it out of my mind, which is easy to do, and just got on with my life. Nobody mentioned we should treat this lump as suspicious until proven otherwise.

Jane Barrett: No I haven’t, I live with my partner who is just the best partner in the world. We’ve travelled a lot, we’ve got a lot of interests, we’ve got some fabulous friends and I have family here and in the UK.

Norman Swan: So when did you decide to find out more about this lump?

Jane Barrett: Well I went bush walking and everything is so subtle, I think you’ve got to sort of understand the subtleness of this, so I’m bush walking, there’s a daily bush walk, it’s a steep climb but it’s a morning walk which takes about an hour. By the end of the holiday I should have been getting better at that walk and just bouncing up this steep slope, but I actually couldn’t walk up this hill. And I noticed I was sleeping a lot but I just put that down to being tired and I was just starting to feel maybe a tiny little bit breathless and I thought well look, I’ll just go and have a check up then I’m going to start on my fitness regime because there are some great bush walks I wanted to do in New Zealand.

So I went back to a different GP who listened to my symptoms and immediately she said ‘you need a fine needle aspiration biopsy, we need to take a little bit of what’s in the lump,’ which hadn’t been suggested before, so I had the aspiration biopsy, then I went to see a specialist.

Norman Swan: And what was the result?

Jane Barrett: Well I went in, I was on my own; again I wasn’t expecting anything too dramatic and he turned around to me and he said—and I call it a triple whammy—he said, ‘You have cancer, you have a cancer that can’t be identified and it’s spread from somewhere in your body’. So that’s the triple whammy, people get diagnosed with cancer, this is a metastatic cancer, that is, it’s spread from somewhere.

Norman Swan: But they don’t know where?

Jane Barrett: And we can’t tell where it’s come from. And then he started talking about possible treatments, right neck dissection, etc. etc, the risk of treatments, the damage to various nerves. I got up, I paid the money, I left, I walked out into the blazing sunshine, I just didn’t know what to do, I was so overwhelmed, I just couldn’t find my car. And I rang my partner and he came home immediately and I told him and we just sort of clung on to each other, we just could not make sense of this.

Norman Swan: Jane Barrett.

Professor David Bowtell is head of Cancer Genomics and Genetics at the Peter MacCallum Cancer Centre in Melbourne.

David Bowtell: We’re talking about a diagnosis of an Unknown Primary Cancer, so the diagnosis is made when a patient presents with disseminated cancer through their body and we don’t know where the cancer originated from.

Norman Swan: Give me a typical story.

David Bowtell: Well there’s a whole spectrum, so at one end of the spectrum are patients who may be elderly and very unwell and have limited clinical workup and it’s difficult to decide, based on that clinical work-up, where the cancer might have originated from. At the other end of the spectrum there’s a 42 year old male who’s otherwise well and presents with just feeling unwell and turns out to have disseminated cancer and has very extensive clinical workup and it’s still unclear where the cancer arose from.

Norman Swan: So you have the biopsy, the pathologist looks at it down the microscope and hasn’t got a clue where it’s come from.

David Bowtell: Exactly.

Norman Swan: And what are the figures?

David Bowtell: It’s in the top ten causes of cancer deaths. In Australia it’s ranked currently around third or fourth, in the UK it’s around about seventh. The reason that that positioning in the ranking changes is that as our technology improves and our ability to diagnose disease improves then some of the unknowns now are becoming known cancers.

Norman Swan: And who has made sense of it for you?

Jane Barrett: That’s a good question. What happened—I went to have various tests, they wanted to try to find out where this cancer had come from so I went through a whole range of tests and I got the feeling I was in a cage and everybody was poking my neck and looking at me. And I just felt that I didn’t want any treatment, I was so overwhelmed and didn’t feel comfortable with the person who was dealing with me. I didn’t want treatment; I was in a total panic and meltdown. And then while I was at one of the centres having the tests, somebody suggested I get a second opinion. I rang this particular group of people, they said they would get back to me, this is a Friday morning, they actually didn’t, then I rang again and I thought I’m due for an operation which I don’t even want, I can’t say, I can’t deal with any of this.

Norman Swan: This was an operation on your neck?

Jane Barrett: On my neck, the right neck dissection yes. And then I rang this number and a man answered and it turned out to be this particular doctor that I am now under. He was just finishing some notes at the end of the day and I told him my problem. He said ‘Come up and see me.’ He sat, he listened. I met somebody instantly that I felt could take me along this dreadful path. Meeting this new person made me believe that I could face dealing with this cancer, and on Friday I wasn’t going to have any treatments. By Monday I was in the Head and Neck Clinic and on Tuesday I was having a more modified approach to see what was going on, to see if they could find any head and neck cancers.

So this person made me act instantly without any referral and helped me to believe that I could face dealing with this cancer.

Norman Swan: You’re listening to the Health Report with me Norman Swan here on RN. A special feature on a neglected but common cancer called Cancer of Unknown Primary, CUP.

Associate Professor Penny Schofield is Scientific Director of the Department for Cancer Experiences Research at Melbourne’s Peter MacCallum Cancer Centre.

Penny Schofield: There are multiple issues that people with CUP face. It’s a very hard to understand diagnosis. People have said, ‘How can you have a cancer and not know where the primary is’? It’s hard to understand, it’s very frightening because doctors are confused about what to do about it. There are very, very few effective treatments, there’s no research to guide diagnosis or treatment and patients end up feeling fairly hopeless, fearful, and I think also almost abandoned by the medical system because the medical system actually doesn’t have any answers.

Norman Swan: And what’s happened to you since?

Jane Barrett: All sorts of incredible things, both good and bad. 2009 March 24th right neck dissection. After I’d left hospital after surgery I was told that I had a massive cancer, I had 70 lymph nodes removed, 47 were cancerous and it was in the tissues. So I left that morning and went to see the radiation oncologist for radiation planning and he said actually we think it might be—from the pathology from the lymph nodes in your neck, we actually think it might be an adenocarcinoma. That could be from lung, bowel or breast etc. And he said 'W.e’d like you to have more tests.’ So I’ve gone for radiation planning and suddenly my world has shifted again, it felt like I was in free fall. And I was thinking but I’ve just had a pile of tests, now it’s a possible other cancer—do I want them to find the primary, will it mean more surgery? My whole world changed. So a whole pile more new tests.

Norman Swan: But still no primary?

Jane Barrett: Still no primary, and I used to sort of dread sitting at home thinking they would call me in saying we’ve found a primary, so I never felt safe until Friday when I thought no one can contact me. Between May and July I had six weeks of radiation to my neck. Now to me an operation was way less scary than radiation. I’m claustrophobic and what they do for a head and neck cancer...

Norman Swan: Put your head in a cage.

Jane Barrett: They put your head in a mask that’s right and you’re enclosed in a room and it’s called a bunker, which has terrible connotations.

Norman Swan: And nobody can stay with you because you’re experiencing radiation.

Jane Barrett: Exactly, so if you can imagine a claustrophobic person strapped, and you can barely open your eyes in the mask as it’s clamped so tightly, I absolutely panicked but the staff were very good.

Norman Swan: And no doubt you went onto the internet and looked up Cancer of Unknown Primary?

Jane Barrett: Well I didn’t feel well enough to do that.

Norman Swan: Psychologically well enough?

Jane Barrett: Psychologically well enough, but I did not know there was a term called Cancer of Unknown Primary, nobody used that term. They said the primary could not be identified. Cancer of Unknown Primary is the overarching cancer group, so I didn’t realise there was a cancer group, although a friend started to see that through the internet. And then the next time I went for radiation planning they said we’ve found a pelvic mass, so again I was absolutely thrown, I just didn’t know what to do.

Norman Swan: And it keeps on getting interrupted by new news.

Jane Barrett: New news.

Norman Swan: And was there a tumour in your pelvis?

Jane Barrett: There was not a tumour. It turned out to be something else and not a problem.

Norman Swan: So you’re on a roller coaster.

Jane Barrett: I wish I could find a word, Norman, yes—roller coaster, free fall—the stress was so enormous.

Norman Swan: And of course they don’t know what to use to treat you because they don’t know what the source of the tumour is.

Jane Barrett: Exactly.

Norman Swan: And did anybody give you a prognosis?

Jane Barrett: I didn’t ask, to me that wasn’t a relevant question. The relevant question was how to deal with the treatments; I’ve seen people who have had poor prognoses who’ve lived, so to me that wasn’t a question that was relevant in my life at that time.

Norman Swan: And now?

Jane Barrett: I know what my prognosis is.

Norman Swan: Jane Barrett.

Dr Linda Mileshkin is a cancer specialist, a medical oncologist at the Peter MacCallum Cancer Centre, and has set up what may well be Australia’s first ever clinic specifically devoted to people with Cancer of Unknown Primary.

Linda Mileshkin: They certainly are patients who stick in your mind because they are so unusual. There is a lady that I saw last year who presented with a lymph node in her armpit and that seemed to be the only site of cancer that she had but it seemed to be a secondary cancer in that location. And so she was very distressed about that because she’d been told by many people that she had incurable cancer and we spent a lot of time trying to look for a primary site and we never found one. But we treated her as though she might have a breast cancer because that seems to be the best approach in that situation and she’s done really well.

We set up the clinic because we realised that there was an unmet need for patients with carcinoma of unknown primary, because Cancer of Unknown Primary is actually quite common and people with this type of cancer were falling through the cracks in the system. There wasn’t any place that those patients really belonged where they could be comprehensively assessed and also where we could set up a research program to improve things for the future.

Norman Swan: And of course this is set against the background that modern cancer care tends to be oriented around people with specific tumours. You know if you’ve got breast cancer you go to a specialised breast cancer clinic, you’ve got colon cancer you go to a bowel cancer clinic.

Linda Mileshkin: Yes, that’s very much the way now particularly in bigger centres like the Peter Mac, that everything is done in a super-specialised environment.

Norman Swan: So if you don’t fit into that mould you’ve got a problem?

Linda Mileshkin: Yes. We also know that Carcinoma of Unknown Primary is also more common perhaps in rural and remote areas where people are not perhaps so well investigated and they may only have some very simple tests, so they might be labelled as Carcinoma of Unknown Primary without actually having a lot of investigation.

Norman Swan: What do we know about the unknown?

David Bowtell: Well not very much.

Norman Swan: Professor David Bowtell again.

David Bowtell: There are very few people who are working on them. They are cancers that challenge the way that we approach the treatment of cancer right from the beginning. So the very first thing you want to know in a cancer patient is where did it come from, is it pancreatic cancer, is it kidney cancer, is it prostate cancer—because it tells us how the patient might fare with their disease and it tells us how best to treat them. With an unknown primary we can’t even get off first base, we don’t know where it came from and therefore how best to treat them.

Norman Swan: Tell me the story of that 42-year-old man, because it is a true story.

David Bowtell: He was actually my first PhD student, a fantastic person and a very talented doctor and he rang me one day and said that he wasn’t feeling great and he’d been to the doctor and distressingly had found that he had disseminated cancer in his lungs and in his liver and elsewhere in his body and they didn’t know where it came from. And at that time we had developed a technology of profiling the activity of thousands of genes simultaneously and it was sort of obvious that maybe we could use this technology to create a database of the gene expression patterns of a large number of known tumours—pancreatic cancers, lung cancers, stomach cancers and so on.

Norman Swan: To see whether or not you could get a genetic signature—if you couldn’t see it under the microscope could you see it through the genes?

David Bowtell: Exactly. What we knew was that the different types of cancers had different signatures and so in principle if we came along with our unknown cancer we could ask whether it matched anything in the database—and it did. In his case it matched actually a lung cancer.

Norman Swan: And what difference did it make to him?

David Bowtell: Actually it made quite a difference to him. He was able to go onto a clinical trial that otherwise he wouldn’t be eligible for because it was a trial specifically for patients with lung cancer and he had a benefit from that clinical trial that allowed him to enjoy what remained of his time with his family.

Norman Swan: Some people have argued that it may not be a cancer of unknown origin, that the cancers you’re looking at when the person first presents are actually multiple primaries of the same origin. In other words it’s not from a distant organ, what you see is what you get.

David Bowtell: Multiple synchronous appearances. We know very little about the biology, we’re pretty sure that these are not a new type of cancer, that they are actually colon cancers, and lung cancers and pancreatic cancers, but what they share is a common biology, a propensity to spread very rapidly, so instead of there being a large primary tumour in the site where it arises, very quickly after it arises it spreads throughout the body, and that makes it very difficult to tell where it’s come from. So they may share some biology that is associated with this rapid metastatic spread, that would be very interesting because that then would present a therapeutic target for us to go after.

Norman Swan: And have you routinely done genetic testing on these tumours and what have you found?

David Bowtell: What we did was we developed in the lab a test that could identify the likely site of origin in a large proportion of the cases. And then we partnered with a pathology company a couple of years ago and a technology transfer company to actually put the test into a proper clinical pathology framework, so that the test would be made available. And that test is about to be released in Australia in the next few weeks.

Norman Swan: So having trialled that test, what proportion of Cancers of Unknown Primary become known to some extent?

David Bowtell: We don’t know the answer to that really well yet. At the moment it’s still at the phase of doing tens of cases, and really what we need are hundreds of cases to really document that accurately. But we think that over half the cases we should be able to get a diagnosis that’s useful. In parallel what we’re doing is to see whether there are molecular changes in these cancers that we can target therapeutically. We’re actually taking two approaches here. One is the traditional approach which is to identify the site of origin and treat accordingly and that’s the basis of the diagnostic test. The other approach is based on where I think we’re going with cancer medicine is to worry less about anatomical location and think more about the molecular changes that have occurred.

Norman Swan: This is the whole notion that some breast cancers molecularly look more like colon cancers than they do other breast cancers?

David Bowtell: Exactly, that’s right. And so we’ve seen for example that some ovarian cancers look like breast cancers molecularly than other ovarian cancers. Others look much more like certain kidney cancers than they do other ovarian cancers and so there’s this whole notion that really what matters is the wiring diagram, not so much where it came from. We’re using next generation DNA sequencing, which is a very, very powerful way of scanning for mutations to see whether there are mutations in these patients, in their tumours, that are actionable. In other words mutations that we have drugs that we could use to target them.

Norman Swan: But even so, even when you know where it’s come from, if a cancer has spread, the results, even using the best technology at the moment without it being cancer of unknown origin are not very good.

David Bowtell: That’s right. One of the things that we’re particularly interested in is understanding how to treat patients in a situation where they’ve relapsed after primary treatment and the cancer has recurred. At the moment we are looking for a whole range of solid cancers we don’t have good ideas about how to manage that. Cancers of Unknown Primary potentially are a unique opportunity to learn how better to treat people in that situation. Ideas that we developed through these molecular profiling strategies could potentially be applied to other more common types of cancers.

Norman Swan: David Bowtell. Here’s Jane Barrett again.

Jane Barrett: I started to feel well after radiation but by November, again this is 2009, I started to feel unwell again, the aching bones came back, the breathlessness, the tiredness and I went to the Ian Gawler Foundation and took part in their ten-day cancer retreat. My partner and I went along together and by the end of a couple of months I got out my walking boots and started a new life. And I believe, I mean some medical people could say ‘well it could just be coincidence’, I believe that the way we dealt with that through the Gawler Foundation, the whole lifestyle change gave me two extra years of well life. I even walked the Six Foot Track, I went walking with camels in the desert, I’ve been to Lake Eyre and had a life where I started to be an advocate and researcher for Cancer of Unknown Primary.

Norman Swan: Jane has been incredible. Despite being extremely ill she has set up a support group, a website, encouraged the production of information resources and been the force behind a major new research study in which Penny Schofield is a principal investigator.

Penny Schofield: Jane really is a quite remarkable woman, she has galvanised the research community to understand that CUP is an under-researched problem and is very important. On the basis of Jane and another consumer who pushed us towards forming this national collaboration and conducting a multi-disciplinary research project to address the issues faced by people with CUP.

Norman Swan: Jane even reviewed your grant.

Penny Schofield: Oh she was instrumental in developing the research ideas and she is a collaborator on the grant so she’s an associate investigator, but she also turns out to be an incredibly good proof reader and proof read the final version.

Norman Swan: So how do you approach it?

Penny Schofield: We are going to establish a cohort of patients who have got a diagnosis of what we call true CUP. These are the people who have had extensive diagnostic work-up, lots and lots of diagnostic tests, but despite all of these tests the primary cancer can’t be found.

Norman Swan: Even within modern genetic testing?

Penny Schofield: Even with modern genetic testing—what they can provide is the best guess location. The aims of this study will be threefold: to provide a better clinical description of the disease, to conduct molecular biological testing, and looking at what are the psychosocial issues that are unique to people who have CUP. The uncertainty that these people feel is unique, there’s a sense of hopelessness and there’s a sense that doctors feel frustrated that they can’t find the tumour and that they can’t provide good treatments for these people. And this sense of frustration I think is communicated to the patients and their families, so I suspect that these patients have a far greater need than actually a lot of other patients. So for instance—and I’m not saying that it’s not terrible having any kind of diagnosis of cancer, it’s a devastating diagnosis—but for instance if you’re diagnosed with breast cancer there’s a whole raft of support mechanisms, there are support groups you can go to, there are survivors you can talk to; but if you’re diagnosed with Cancer of Unknown Primary, most people have never even heard of this type of cancer and there aren’t those kind of support mechanisms.

Jane Barrett: At the end of 2011 I started to feel unwell, I could feel things changing and the cancer had spread and I needed a further operation, which I had to my neck. It also showed that I had metastatic spread in my chest. I was admitted as an emergency with an abdominal blockage where the tumour has now spread to my abdomen. And when I look at the options, I have Cancer of Unknown Primary, so what’s the point of throwing all sorts of treatments at something you don’t know what you’re throwing at. You could go on cutting my body open for bits that don’t work... So in the end I’ve decided that I will take the palliative care approach. Now each day is a bonus. I talk openly to friends about dying, about what I want done, how I’m setting up things for after my death around arranging my website and organising my network that I’ve set up called CUP Action.

Norman Swan: You’re sounding remarkably up, given you are in a dark place.

Jane Barrett: Yes. I think I’ve had so much to deal with, there were some days when I felt I was going to die and I’ve gone through many meltdowns, but I’ve done my advanced care directive about what I want and the conditions of that advanced care directive. The process is utterly surreal, I could hardly believe this is me at the end of my life. It’s very hard to contemplate, so I probably don’t focus on that, I focus on the friends who come and make me food and keep me company and write lovely things to me. And I focus on being with my partner, who has been the most wonderful, wonderful partner a person could want. I’m sure there will be meltdowns and terrors and fears.

Norman Swan: And all because of a mysterious cancer that no one knows very much about.

Jane Barrett: Exactly. And most people in the community have no understanding that this is the fifth most common cause of cancer deaths, it’s the seventh most common cause of cancer diagnosis in women, the ninth in men. No one has ever heard of it, no one has advocated for it because most people with this cancer die within the first year. So I took it upon myself to try and get a better deal and to bring this cancer from its invisibility to its visibility. And there is now what I would call a CUP community, there are people taking on this cancer—it was invisible.

Norman Swan: And what would you like your legacy to be?

Jane Barrett: You’re going to make me cry in a minute Norman, that I’ve been a good friend to people, to my friends, that I’ve been a good partner to my partner. This is the loneliest cancer, that Cancer of Unknown Primary is taken up, it’s given the funding it deserves, patients are given the support that they need, that we take on Cancer of Unknown Primary like we’ve taken on all the other named cancers. Its impact is huge, the stress that people feel. One young woman said to me I didn’t know there was anybody else alive with this cancer, and I said yes, I’m alive and I’m trying to do something.

My legacy would be the funding, this cancer dealt with, known in the community, that the doctors aren’t failing to find the primaries, that people are not left alone and frightened and unsupported—that’s what I would like and that I would have played some part in that.

Norman Swan: Jane thank you for being so courageous to talk to us.

Jane Barrett: Thank you Norman, this orphan of the cancer world is getting attention finally.

Norman Swan: The amazing Jane Barrett, I’m Norman Swan, you’ve been listening to the Health Report, a special feature on Cancer of Unknown Primary.

Guests

Jane Barrett

Patient with CUPSydney

Professor David Bowtell

Head of Cancer Genomics and GeneticsPeter MacCallum Cancer CentreMelbourneVictoria